Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT.

Community-associated Clostridium difficile infection (CA-CDI) now accounts for approximately 50% of CDI cases in central Minnesota; animals and meat products are potential sources. From November 2011 to July 2013, we cultured retail meat products and fecal samples from food-producing and companion animals in central Minnesota for C. difficile by using standard methods. The resulting 51 C. difficile isolates, plus 30 archived local veterinary C. difficile isolates and 208 human CA-CDI case isolates from central Minnesota (from 2012) from the Minnesota Department of Health, were characterized molecularly, and source groups were compared using discriminant analysis. C. difficile was recovered from 0 (0%) of 342 retail meat samples and 51 (9%) of 559 animal fecal samples. Overall, the 81 animal source isolates and 208 human source isolates were highly diverse genetically. Molecular traits segregated extensively in relation to animal versus human origin. Discriminant analysis classified 95% of isolates correctly by source group; only five (2.5%) human source isolates were classified as animal source. These data do not support meat products or food-producing and companion animals as important sources of CA-CDI in the central Minnesota study region.

A multi-agency workshop was held from 25 to 27 August 2009, at the National Institute of Standards and Technology (NIST), to identify and prioritize the development of radioanalytical Certified Reference Materials (CRMs, generally provided by National Metrology Institutes; Standard Reference Materials, a CRM issued by NIST) for field and laboratory nuclear measurement methods to be used to assess the consequences of a domestic or international nuclear event. Without these CRMs, policy makers concerned with detecting proliferation and trafficking of nuclear materials, attribution and retribution following a nuclear event, and public health consequences of a nuclear event would have difficulty making decisions based on analytical data that would stand up to scientific, public, and judicial scrutiny. The workshop concentrated on three areas: post-incident Improvised Nuclear Device (IND) nuclear forensics, safeguard materials characterization, and consequence management for an IND or a Radiological Dispersion Device detonation scenario. The workshop identified specific CRM requirements to fulfill the needs for these three measurement communities. Of highest priority are: (1) isotope dilution mass spectrometry standards, specifically (233)U, (236g)Np, (244)Pu, and (243)Am, used for quantitative analysis of the respective elements that are in critically short supply and in urgent need of replenishment and certification; (2) CRMs that are urgently needed for post-detonation debris analysis of actinides and fission fragments, and (3) CRMs used for destructive and nondestructive analyses for safeguards measurements, and radioisotopes of interest in environmental matrices. (2012 Akademiai Kiado, Budapest, Hungary.)

Diagnostic tests for detecting emerging influenza virus strains with pandemic potential are critical for directing global influenza prevention and control activities. In 2008, the Centers for Disease Control and Prevention received US Food and Drug Administration approval for a highly sensitive influenza polymerase chain reaction (PCR) assay. Devices were deployed to public health laboratories in the United States and globally. Within 2 weeks of the first recognition of 2009 pandemic influenza H1N1, the Centers for Disease Control and Prevention developed and began distributing a new approved pandemic influenza H1N1 PCR assay, which used the previously deployed device platform to meet a >8-fold increase in specimen submissions. Rapid antigen tests were widely used by clinicians at the point of care; however, test sensitivity was low (40%-69%). Many clinical laboratories developed their own pandemic influenza H1N1 PCR assays to meet clinician demand. Future planning efforts should identify ways to improve availability of reliable testing to manage patient care and approaches for optimal use of molecular testing for detecting and controlling emerging influenza virus strains.